NM_000621.5:c.*121G>A

Variant names:

• chr13-46834716-C-T
• rs3125
• NM_000621.5:c.*121G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000621.5(HTR2A):​c.*121G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HTR2A NM_000621.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 25 publications found

Genes affected

HTR2A (HGNC:5293): (5-hydroxytryptamine receptor 2A) This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	NM_000621.5	MANE Select	c.*121G>A		3_prime_UTR	Exon 4 of 4	NP_000612.1
	HTR2A	NM_001378924.1		c.*121G>A		3_prime_UTR	Exon 4 of 4	NP_001365853.1
	HTR2A	NM_001165947.5		c.*121G>A		3_prime_UTR	Exon 3 of 3	NP_001159419.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.*121G>A		3_prime_UTR	Exon 4 of 4	ENSP00000437737.1
	HTR2A	ENST00000543956.5	TSL:1	c.*121G>A		3_prime_UTR	Exon 3 of 3	ENSP00000441861.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 555616 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 289878

African (AFR) AF: 0.00 AC: 0 AN: 14458

American (AMR) AF: 0.00 AC: 0 AN: 19754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14442

East Asian (EAS) AF: 0.00 AC: 0 AN: 32640

South Asian (SAS) AF: 0.00 AC: 0 AN: 46750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3362

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 359972

Other (OTH) AF: 0.00 AC: 0 AN: 29580

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 66

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.74
PhyloP100		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3125; hg19: chr13-47408851;